The feasibility of totally implantable circulatory support and replacement systems depends on the ability of the body to dissipate the rejected heat from the power source driving the blood pump. The effects of the interfacial temperature of 41 degrees C to 45 degrees C on components involved in host defense, tissue healing and foreign body reaction are, however, largely unknown. Our preliminary in vitro experiments showed temperature dependent suppression of immunocompetent cells and tissue repair cells. Chronic and continuous heat dissipation into the body creates a new biological and medical problem. Recent chronic in vivo experiments in calves implanting heating devices with constant heat fluxes showed persistent inflammatory reaction, thick tissue capsule formation, and necrosis in the tissue capsule itself and adjacent organs at far lower heat fluxes than those previously thought to be acceptable. It was also found that a considerable difference in interface temperature exists between the muscle and lung tissues in dissipating the same amount of heat. In addition, phagocytic, chemotactic, and random migration functions of circulating leukocytes were suppressed in animals which received more than a 0.08W/cm2 heat flux. When the power input was controlled to yield constant heater surface temperature, the heat flux necessary to maintain that temperature increased with time for temperatures above 42 degrees C. This suggested the presence of some heat adaptation mechanism. Still, it is necessary to perform further studies in which tissue temperature and perfusion can be measured in vivo. Concurrently, heat effects on crucial cellular and immune components must be determined. In this way, an analytical model of the tissues' response to heat may be formulated. The specific aims of this proposed program are: (1) to investigate the effects of chronic heating on biological components crucial to systemic and local heat defense, wound healing, and surface interactions; (2) to determine the in vivo temperature distribution response to chronic heat generated by an implanted device, to identify the safe range of high temperature, and the corresponding tissue reactions, and (3) to develop a mathematical model of the tissue temperature distribution which incorporates both long- and short-term adaptation mechanisms to heat through angiogenesis and increased perfusion, respectively. The information obtained in the proposed studies will be invaluable not only for currently ongoing artificial heart programs, but also for future application of chronic hyperthermia for cancer patients.